Lung cancer is the leading cause of cancer related deaths in males and females in the United States. Surgical resection remains the only curative therapy for patients with non-small cell lung cancer (NSCLC). However, despite undergoing curative resection, a large percentage of patients with node negative NSCLC still develop recurrent disease. Thus, improvements in early detection are essential for improving the survival in patients with NSCLC. This study aims to use the power of molecular biology to develop and test new molecular markers for the early detection of NSCLC. As an interactive project, this study brings together promising new approaches from various investigators to develop new molecular markers garnished from the most promising areas of genetic research. Novel molecular markers will be developed by 1) the identification of tumor markers through serial analysis of gene expression (SAGE); 2) discovery of additional hypermethylated gene promoter regions for PCR based detection; and 3) identification of hypermutable sequences in mitochondrial DNA (a novel method of nucleic acid based detection). By integrating these promising approaches from diverse labs at John's Hopkins, we will develop a comprehensive profile of novel molecular markers. Using our available samples, we will be able to determine the timing of these molecular markers in lung cancer progression. We also have at our disposal a unique set of paired Bronchoalveolar Lavage (BAL) and serum samples from lung cancer patients allowing us to test newly identified markers outlined in this proposal. These critical resources will allow us to characterize newly developed markers for rapid translation in the clinical setting through the extended components of the early detection research network. Unlike the usual approach based on isolated investigators, this integrated approach will emphasize sharing of subjects, tissue samples, resources, technical expertise, and data analysis strategies. Our integrated effort will not only offer clinical direction for basic research efforts, but will also facilitate a direct translation of novel technology from the basic laboratory into clinical arena.